isocitrate dehydrogenase (idh)

Ivosidenib (AG-120) is an orally available inhibitor of isocitrate dehydrogenase type 1 (IDH1) with potential antineoplastic activity. It specifically inhibits a mutated form of IDH1 in the cytoplasm, preventing the formation of the oncometabolite 2-hydroxyglutarate (2 hG), which may induce cellular differentiation and inhibit cellular proliferation in IDH1-expressing tumor cells.

Mutant IDH1-IN-2 is an inhibitor of mutant Isocitrate dehydrogenase (IDH) proteins, with an IC50 of 16.6 nM in fluorescence biochemical assay and an IC50 of <22 nM in LS-MS biochemical assay.

AGI-6780 is a potent and selective inhibitor of IDH2 R140Q mutant.

Mutant IDH1-IN-1 is a potent inhibitor of the mutant IDH1 R132 h, exhibiting an IC50 of less than 0.1 μM.

Olutasidenib (FT-2102) is under the study in the treatment of acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). Olutasidenib is a highly effective, brain penetrant, and selective inhibitor of the mutant Isocitrate dehydrogenase 1 (IDH1) (IC50: 21.2 nM and 114 nM for IDH1- R132H and IDH1- R132C, respectively).

Mutant IDH1 inhibitor is an effective inhibitor of mutant IDH1 R132H (IC50: < 72 nM).

DS-1001b is an inhibitor of mutant IDH-1 (Isocitrate Dehydrogenase-1)

BAY-1436032 is a novel, selective and orally available inhibitor of pan-mutant isocitrate dehydrogenase 1 (IDH1).

Vorasidenib (PVM/MA) is an inhibitor of mutant isocitrate dehydrogenase (IDH; IC50s = 31.9 and 31.7 nM for IDH1R132H and IDH2R140Q, respectively)

Enasidenib (AG-221) is an orally available inhibitor of specific mutant forms of the mitochondrial enzyme isocitrate dehydrogenase type 2 (IDH2), with potential antineoplastic activity.

AGI-5198 (IDH-C35) is a potent and selective inhibitor of IDH1 R132H and R132C mutants, with IC50 values of 0.07 μM and 0.16 μM, respectively.

IHMT-IDH1-053 (compound 16) is an irreversible inhibitor highly selective for the IDH1 R132H mutant, with an IC50 of 4.7 nM. It preferentially targets IDH1 mutants over wild-type IDH1 and IDH2, in both their wild-type and mutant forms. In 293T cells transfected with the IDH1 R132H mutant, IHMT-IDH1-053 reduces 2-hydroxyglutarate (2-HG) production with an IC50 of 28 nM. The compound binds to the R132H protein at an allosteric site near the NADPH binding region, forming a covalent linkage with Cys269. Additionally, IHMT-IDH1-053 inhibits the growth of both the HT1080 cell line and primary acute myeloid leukemia (AML) cells harboring IDH1 R132 mutations [1].

Alternaphenol B2, a selective inhibitor of mutant isocitrate dehydrogenase 1 (IDH1m), is sourced from the coral-derived fungus Parengyodontium album SCSIO SX7W11. It exhibits inhibitory activity specifically against the IDH1 R132H mutation, with an IC50 of 41.9 μM [1].

Isocitrate dehydrogenase (ICDH), a critical enzyme in the citric acid or tricarboxylic acid cycle, facilitates the oxidative decarboxylation of isocitrate to α-ketoglutarate while reducing NAD(P)+ to NAD(P)H, thus playing pivotal roles in cellular metabolism [1].

Mutant IDH1-IN-6 is an orally active compound that effectively inhibits mutant isocitrate dehydrogenase (IDH) enzymes. It demonstrates potency and selectivity, with IC50 values of 6.27, 3.71, 36.9, and 11.5 nM for IDH1 R132H, IDH1 R132C, IDH2 R140Q, and IDH2 R172K mutants, respectively. Notably, Mutant IDH1-IN-6 exhibits lower activity in inhibiting wild-type IDH enzymes.

Mutant IDH1-IN-4 is an mutant Isocitrate dehydrogenase 1 (IDH 1) inhibitor.

IDH889 is a brain penetrant, an allosteric and mutant specific IDH1 inhibitor. IDH889 has effective selectivity for IDH1 R132* mutations (IC50s: 0.02 μM, 0.072 μM, and 1.38 μM for IDH1R132H, IDH1R132C, and IDH1wt).

IDH-305 is an orally available, mutation-selective, and brain-penetrant IDH1 inhibitor targeting the IDH1 (R132) mutation. It is 200-fold more selective for mutant IDH1 isoforms than wild type, with IC50s of 27 nM, 28 nM, and 6.14 nM for IDH1R132H, IDH1R132C, and IDH1WT, respectively.